Insulin on Muscle Flashcards
What are the types of glucose transporter?
SGLT
GLUTs
How many TM domains does the SGLT have?
14
What part of the SGLT binds the sugar?
C-terminus
How does the SGLT work?
Na binds a negative charge in the transporter, opens up for glucose, glucose binds causing conformational change and the release of glucose and Na on the other side
What are the transporters on the basolateral membrane of the gut?
Na-K ATPase
GLUT2
What are the features of GLUTs?
present on the surface of all cell membranes
transport glucose down a concentration gradient
energy dependent process
can operate bi-directionally as long as down the gradient
What are the classes of GLUTs?
Class I
Class II
Class III
What are the features of the gluts in class I?
1,3,4 are all high affinity
2 is low affinity
they all transport glucose
What are the features of the gluts in class II?
5,7,9,11 and HMIT1
low affinity for glucose, transport fructose
What are the features of the gluts in class III?
6,8,10,12
not really sure yet
How many TM domains do GLUTs have?
12
Where is GLUT1 generally found?
ubiquitously
Where is GLUT2 generally found?
kidney, sm. intesting, liver, pancreatic b cells
Where is GLUT 3 found?
neurons and placenta
Where is GLUT 4 found?
skeletal muscle, cardiac muscle, adipose tissue
Where is GLUT 4 found?
skeletal muscle, cardiac muscle, adipose tissue
What is GLUT4 responsible for?
the response to insulin
What is cytochalasin B?
a fungal metabolite called CB which binds to GLUTs in a non-competitive manner
What is useful about CB?
It gives you a 1:1 molar ratio to the number of transporters present
What can be observed with insulin treatment?
translocation of transporters from the Intracellular membrane to the plasma membrane
How can the translocating transporter be identified?
with antibodies and GFP
Why is this finding important?
muscle is the principal tissue for glucose use in the fed state
muscle is a primary target of insulin
muscle must be fully responsive to insulin in order to lower blood glucose
What does phosphorylation of the insulin receptor cause?
phosphorylation of docking proteins such as IRS-1,2,3,4
What does phosphorylation of docking proteins cause?
activation of signalling pathways PI3K, PKB, MAPK, p70S6
What does activation of the signalling pathways cause?
glucose transport, glycogen synthesis, lipogenesis, protein synthesis, gene expression, cellular growth
What does Insulin cause in muscle?
increase glucose up take
increase glucose use -> glycogen and glycolysis
increase amino acid uptake
increase protein synthesis, decreased protein breakdown
What is the skeletal muscle glucose uptake during exercise regulated by?
glucose supply, glucose transport
glucose phosphorylation
How does glucose phosphorylation maintain the concentration gradient?
It cannot exit the cell, so glucose can keep coming in
How does exercise simulate the effects of insulin?
increases the translocation of GLUT 4 via AMPK
What does Metformin do?
suppresses hepatic glucose production
increases muscle glucose uptake
inhibits complex 1 of respiratory chain
What shares the metabolic effect of Metformin?
AICAR
